on February 18, 2002
Published online before print February 18, 2002, doi: 10.1161/hc1002.105136
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Submitted on September 10, 2001
From the National Health and Medical Research Council Clinical Trials Centre (R.J.S., I.C.M., W.H, A.K.), University of Sydney, Sydney; Royal Melbourne Hospital (D.H.), Melbourne; University of Queensland (D.C.), Brisbane; Royal Prince Alfred Hospital (D.S.), Sydney; University of Otago (R.A.H.S.), Dunedin; Sir Charles Gairdner Hospital (P.T.), Perth; Green Lane Hospital (H.W.), Auckland; and National Heart Foundation (J.S., A.T.), Melbourne, Australia. * To whom correspondence should be addressed. E-mail: enquiry{at}ctc.usyd.edu.au.
Background—The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trial showed that pravastatin significantly reduced mortality and coronary heart disease (CHD) events in 9014 patients with known CHD and total cholesterol 4.0 to 7.0 mmol/L at baseline. Secondary objectives included assessment of CHD event reduction according to lipid levels. Methods and Results—We investigated the relationships of baseline and on-study lipids with subsequent CHD events in separate Cox models. Treatment effect on CHD event reduction was examined by baseline lipids and after adjustment for on-study lipid levels. Baseline lipids were significant predictors of CHD events. The adjusted relative risk per mmol/L (on placebo) was 1.24 (P=0.004) for total cholesterol, 1.28 (P=0.002) for low-density lipoprotein cholesterol, and 0.52 (P=0.004) for high-density lipoprotein cholesterol. Apolipoproteins A1 and B were strong predictors (each P=0.001). Pravastatin reduced the risk of the composite outcome of fatal CHD or nonfatal myocardial infarction by 24% (95% confidence interval [CI], 15% to 32%) and the expanded end point of fatal CHD, nonfatal myocardial infarction, unstable angina, or coronary revascularization by 17% (95% CI, 10% to 24%). Similar relative effects were observed for different categories of baseline lipids. The proportion of treatment effect explained by on-study lipid levels was 67% (95% CI, 27% to 106%) for the composite and 97% (95% CI, 49% to 145%) for the expanded end point. The most important lipids associated with event reduction were apolipoprotein B, low-density lipoprotein cholesterol, and the combination of total and high-density lipoprotein cholesterol. Conclusions—Changes in lipid levels can explain all or most of the observed benefit of pravastatin. Some treatment effect may also be mediated through nonlipid changes.
Revised on December 28, 2001
Accepted on January 2, 2002
Relationship Between Lipid Levels and Clinical
Outcomes in the Long-Term Intervention With Pravastatin in
Ischemic Disease (LIPID) Trial. To What Extent Is the Reduction in
Coronary Events With Pravastatin Explained by
On-Study Lipid Levels?
R. John Simes MD*,
Key words: lipids • coronary disease • atherosclerosis • apolipoproteins • cholesterol
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